The juvenile brain exhibits a high capacity for plasticity and repair that is severely restricted in adulthood. In the juvenile brain, there is a biological “critical period,” when the brain is extraordinarily adaptable. The older brain, however, instead of easily re-molding itself to accommodate new kinds of inputs, is more constrained. This waxing and waning of cortical plasticity during a postnatal critical period serves to consolidate neural circuits and behavior, but in turn limits recovery of function in the adult brain.
For example, discordant vision through the two eyes during an early critical period results in the enduring loss of visual acuity (amblyopia) that reflects aberrant circuit remodeling within primary visual cortex (V1). Amblyopia, which affects 2 to 4% of the human population, exhibits little recovery in adulthood (H. Morishita, T. K. Hensch, Curr. Opin. Neurobiol. 18, 101 (2008)).
Thus, experience-dependent brain plasticity declines after an early critical period during which circuits are established. Loss of plasticity with closure of the critical period limits improvement of function in adulthood, but the mechanisms that change the brain's plasticity remain poorly understood.
While many processes contribute to this change in the brain's learning potential, there is evidence suggesting that some of the changes are brought about by the gradual accumulation of molecules that limit the brain's adaptability. It is believed that rather than silencing neurons outright, these molecules help hold them in check, suppressing their tendency to grow and otherwise change with experience. The only molecules previously reported to play a role in closing the critical period are related to axonal growth inhibition, such as chondroitin sulfate proteoglycans and the myelin-signaling proteins NgR and PirB (T. Pizzorusso et al., Science 298, 1248 (2002); A. W. McGee, Y et al., Science 309, 2222 (2005); J. Syken, T., et al., Science 313, 1795 (2006)).
Accordingly, there is a need in the art for the identification of molecules that restrict adult plasticity, modulation of which would be of benefit to injured or dysfunctional adults to permit recovery of neurological performance.